Physiology of Positive Pressure Breathing

Spontaneous breathing in normal patients is based on the initiation of negative intrathoracic pressure and is mediated by contraction and relaxation of the diaphragm. Contraction of the diaphragm decreases pressure in the chest cavity and results in inhalation, whereas relaxation of the diaphragm and recoil of the chest wall increase pressure in the chest cavity and result in passive exhalation. The amount of force required to generate adequate inspiration is influenced by the work of breathing; when work of breathing increases, patients may be unable to generate enough negative force to sustain successful respiration and will require ventilatory support. Unlike spontaneous breathing, both invasive and noninvasive mechanical ventilation are based on the delivery of humidified air with positive pressure. The amount of positive pressure required for adequate ventilation is dependent on the patient’s respiratory effort, ranging from mild assistance to full support. “Inhalation” occurs by driving air into the lungs under positive pressure; air is passively exhaled owing to chest wall recoil.

Transition from negative pressure breathing to positive pressure breathing affects cardiovascular and pulmonary physiology and can have significant clinical consequences. Pressure changes in the thoracic cavity directly affect pressures in the chambers of the heart. During spontaneous inspiration, venous return and preload are augmented, cardiac output is increased, and there is an increased pressure gradient between the left ventricle and the aorta. With the initiation of positive-pressure ventilation (PPV), venous return is diminished, cardiac output falls, and there is a decreased pressure gradient between the left ventricle and the aorta.¹ Relative hypotension can occur after ventilatory support has been initiated, and this may be exaggerated in patients with clinical hypovolemia or vasodilatory states.²

Invasive Mechanical Ventilation

The primary considerations regarding initiation of mechanical ventilation relate to how each breath should be delivered. This includes how a “breath” is defined, how large it should be, how fast it should be delivered, how often it should be delivered, and how to manage the interaction of the patient with the ventilator.

How the ventilator defines a breath is referred to as the control variable. The ventilator can give breaths based on delivery of a set pressure or a set volume, referred to as pressure-controlled ventilation (PCV) and volume-controlled ventilation (VCV), respectively. The amount of time over which the breath is delivered is defined as the inspiratory time, and the rate at which air travels through the circuit is defined as inspiratory flow.

In PCV, a set amount of pressure is applied to the airway to expand the lungs. When the target pressure is reached, gas delivery ends and passive exhalation is permitted. During PCV, target pressure and inspiratory time are set, whereas the delivered tidal volume and inspiratory flow vary as functions of dynamic lung compliance and airway resistance. Ability to control the pressure delivered to the lungs is particularly useful to prevent barotrauma (see later). In addition, because inspiratory flow is not fixed, PCV may improve ventilator synchrony in intubated patients with a high respiratory drive. A significant disadvantage of PCV is that tidal volume cannot be guaranteed or limited and can change with acute changes in lung compliance. PCV offers advantages over VCV in clinical conditions in which control of airway pressure is strictly mandated. This includes patients with the potential to develop dynamic hyperinflation and intrinsic positive end-expiratory pressure (PEEP), such as patients with severe asthma or those with respiratory failure from chronic obstructive pulmonary disease (COPD).

In VCV a breath is defined by delivery of a set tidal volume to the lungs. Inspiratory flow is fixed, and inhalation ends when a preset tidal volume has been delivered; peak inspiratory pressures (PIPs) and end-inspiratory alveolar pressures vary based on lung compliance and set tidal volume. The main benefit to VCV is the ability to control tidal volume and minute ventilation, but it may be problematic by causing high peak pressures when the compliance of the respiratory system is poor. Clinically, poor respiratory system compliance occurs in conditions that increase lung or chest wall stiffness. Such conditions include pulmonary edema, acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), pneumothorax, and obesity.³

When a physician is choosing between pressure-cycled ventilation versus volume-cycled ventilation, it is important to consider the underlying reason for mechanical ventilation. Volume-cycled ventilation should be used when strict control of tidal volume is mandated. Specifically, this includes patients with known ALI or ARDS, in whom low–tidal volume strategies have been proven to reduce mortality.⁴ In addition, patients with decreased chest wall compliance should be placed on VCV to ensure that adequate tidal volume is delivered. This includes patients with morbid obesity or severe chest wall burns. Conversely, in conditions in which strict control of airway pressure is desired, pressure-cycled ventilation should be used. As detailed earlier, this includes patients with asthma or COPD. In addition, because inspiratory flow is not limited in pressure-cycled ventilation, this strategy may be preferred to volume-cycled ventilation in patients with a high respiratory drive, such as patients with salicylate overdose. For patients who do not require strict control of either pressure or volume, similar ventilation mechanics can generally be achieved with either pressure-cycled or volume-cycled ventilation (Table 2-1).

Newer ventilators are able to deliver breaths that combine volume and pressure strategies, referred to as dual-control ventilation. A common dual-control method of ventilation is pressure-release volume control (PRVC). A variation of volume control, PRVC is set to deliver a specific tidal volume while simultaneously minimizing airway pressure. Unlike with strict volume control, pressure is measured and modulated by the ventilator with each breath to ensure the delivery of the preset tidal volume. In addition, a pressure limit is set, and the ventilator sounds an alarm when that pressure has been exceeded. Theoretically, this combines the advantages of pressure and volume control to ensure the delivery of a specific tidal volume while the airway pressure is monitored. That said, because the ventilator is set to deliver a specific tidal volume, the disadvantages of volume-cycled ventilation persist. In addition, elevations in airway pressure are still possible and must be addressed if acute changes in respiratory system compliance occur. This mode of ventilation has not been specifically studied but likely does not offer significant advantage over traditional volume- or pressure-cycled ventilation, particularly if strict parameters for airway pressure are desired.

Ventilator mode refers specifically to the amount of respiratory support provided by the ventilator but more commonly represents a combination of the type of breath to be given and the way the breath is to be initiated. The most common ventilator modes can be categorized on the basis of how often the ventilator will initiate a breath for the patient and can be divided broadly into continuous mechanical ventilation (CMV), intermittent mechanical ventilation (IMV), and continuous spontaneous ventilation (CSV).⁵ CMV and IMV can be delivered via pressure-control or volume-control methods. In CSV, no mandatory breaths are delivered to a patient; the size of the breath is determined by the effort of the patient and can be augmented with applied pressure to the airway. These methods are compared in Table 2-2. Other, more complex modes of ventilation include proportional-assist ventilation (PAV) and airway pressure release ventilation (APRV), though these generally are not used in the emergency department (ED).

CMV is intended to provide full ventilatory support for patients with little or no spontaneous respiratory activity. CMV, also referred to as assist-control (A/C) ventilation, provides a preset number of breaths per minute. In addition to preset breaths, A/C will also deliver a breath in response to patient effort. In this mode, patients can trigger a breath at any rate but will always receive at least the preset number of breaths. Notably, when a patient initiates a breath, he or she receives the full breath as set on the ventilator. For the promotion of ventilator synchrony, a spontaneous patient-initiated breath will take priority over a preset breath, meaning that if the ventilator is set to deliver 12 breaths/min, a breath is provided every 5 seconds in the absence of spontaneous inspiratory effort. When the patient makes a spontaneous effort, the ventilator provides an additional breath and the timer resets for another 5 seconds. A/C ventilation is the most useful initial mode of mechanical ventilation in ED patients, as many patients are initially paralyzed and sedated and do not interact with the ventilator. One of the biggest challenges with A/C ventilation, however, is that patient-initiated breaths are not proportional to patient effort; when inspiratory effort is detected, a full-sized breath is delivered. Clinically, this requires adequate sedation of patients when ventilated in A/C mode to prevent spontaneous respiratory efforts that will result in hyperventilation, air trapping, hypotension, and poor ventilator synchrony.⁶

Synchronized intermittent mandatory ventilation (SIMV) provides intermittent ventilatory support to patients by delivering both mandatory and spontaneous breaths. In SIMV, a mandatory breath is given at a preset rate, but the breath is synchronized as much as possible with spontaneous patient effort. Much as with A/C, the patient will receive at least the minimum number of preset mandatory breaths; if the patient provides no effort, the preset number of breaths will be given. If a patient has a rate of spontaneous respirations lower than the set rate, the ventilator will provide the preset number of full breaths but will deliver as many as possible in synchrony with patient effort. In these scenarios there is little difference between A/C and SIMV. If a patient has a rate of spontaneous respirations higher than preset rate, the patient receives all preset full breaths at the set rate, but additional breaths generated by the patient will be commensurate with his or her respiratory effort. Additional breaths can be given via pressure support (see later). SIMV is useful in patients who are sedated but who have weak respiratory efforts and combats some of the challenges of using A/C in awake patients. Delivery of extra breaths consistent with patient respiratory effort attenuates the effects of air trapping and hyperventilation and may promote patient comfort.

CSV, in contrast to A/C or SIMV, delivers a breath only on patient-initiated trigger. Pressure-support ventilation (PSV) is designed to support patients’ spontaneous respiratory effort by delivering an applied pressure to the airway on the trigger of a breath. The amount of pressure required to support a full breath is variable and depends on the patient’s ability to overcome the work of breathing. When inspiratory flow stops, signaling the end of inhalation, pressure support ceases and exhalation is allowed to proceed spontaneously. The level of pressure support is the only parameter determined by ventilator settings: inspiratory flow, inspiratory time, and tidal volume are determined by the patient effort. This mode of ventilation most closely resembles normal spontaneous breathing and for this reason promotes patient control and comfort. In the ED, PSV is rarely used for intubated patients because most patients who require intubation are unable to effectively breathe spontaneously and may have failed noninvasive support before intubation. PSV may prove most useful in awake and interactive patients who have been intubated for temporary airway protection rather than for respiratory failure. If PSV is used, careful monitoring and ventilatory alarms are needed to ensure against undetected hypoventilation or apnea.

Noninvasive Techniques

Noninvasive positive-pressure ventilation (NPPV) is the delivery of CSV via sealed mask rather than endotracheal tube. As with PSV, the ventilator is set to provide a defined level of pressure when a patient takes a breath; inspiratory flow and inspiratory time are completely patient mediated. The most common types of noninvasive ventilation in the ED are continuous positive airway pressure (CPAP) and bi-level positive airway pressure (BL-PAP). BiPAP, a term commonly used for BL-PAP, is the proprietary name of a portable device that uses this method of noninvasive ventilation rather than a term for the ventilation itself (Philips Respironics, Murrysville, Pa.). CPAP provides constant positive pressure throughout the respiratory cycle, whereas BL-PAP alternates between higher pressure during inspiration (IPAP) and lower pressure during expiration (EPAP). Although, strictly speaking, CPAP applies positive pressure to the airway during inspiration, the amount of inspiratory assistance is minimal. Conversely, just as with invasive mechanical ventilation, IPAP augments patient respiratory effort by decreasing the work of breathing during inspiration, whereas EPAP acts as PEEP to maintain FRC and alveolar recruitment. Notably, although PEEP, CPAP, and EPAP all represent positive airway pressure at the end of expiration, PEEP by convention refers to pressure applied during invasive mechanical ventilation, whereas CPAP is the application of positive pressure (invasively or noninvasively) during spontaneous breathing. The terms are occasionally used interchangeably.

General Approach: Noninvasive versus Invasive Ventilation

The decision to intubate carries significant implications for patients, including potentially life-threatening complications related to airway management and subsequent complications related to intensive care unit (ICU) care.⁸ NPPV is an appealing option for patients requiring ventilatory assistance with potentially reversible conditions when tracheal intubation is not immediately necessary, or as a therapeutic adjunct for patients with “do-not-intubate” directives.^9,10 In appropriately selected patients, NPPV obviates intubation in greater than 50% of cases and improves survival.^8,11 Need for emergency intubation is a contraindication to NPPV, except as a means to improve preoxygenation in preparation for intubation. Other relative contraindications include decreased level of consciousness, lack of respiratory drive, increased secretions, hemodynamic instability, and conditions, such as facial trauma, that would prevent an adequate mask seal.^12,13 If NPPV is initiated, patients should be reassessed frequently for progress of therapy, tolerance of the mode of support, and any signs of clinical deterioration that indicate a need for intubation.

Patients most likely to respond to NPPV in the ED are those with more readily reversible causes of their distress, such as COPD exacerbation or cardiogenic pulmonary edema in which fatigue is a significant factor. Robust evidence suggests benefit of NPPV for both conditions. In patients with acute COPD exacerbations, NPPV decreases the need for subsequent intubation, hospital length of stay, and mortality when compared with standard therapy. Notably, though helpful in most patients with COPD exacerbation, NPPV has been shown to have the largest benefit for patients with hypercapnic acidosis and pH below 7.3.14–17 Treatment failure, defined as subsequent need for intubation, is predicted by a Glasgow Coma Scale score of less than 11, a sustained arterial pH less than 7.25, and tachypnea greater than 30 breaths/min.¹⁸

In patients with acute cardiogenic pulmonary edema (ACPE), NPPV reduces the work of breathing while simultaneously improving cardiac output; application of NPPV causes elevations in intrathoracic pressure that decrease both left ventricular (LV) ejection pressure and LV transmural pressure. This results in afterload reduction. In addition, decreases in RV preload may improve LV compliance via ventricular interdependence.1–3,19,20 Compared with standard therapy, multiple studies and several meta-analyses have confirmed decreased need for intubation as well as decreased mortality for patients with ACPE treated with NPPV. Benefits were independent of whether patients received CPAP or BL-PAP, and despite suggestions from early clinical data, no increased rate of acute myocardial infarction occurred in patients receiving any form of NPPV.^21–24 Though either modality can be used, a recent ED-based study suggested faster clinical improvement with BL-PAP.²⁵ Specific predictors of failure of NPPV in congestive heart failure (CHF) have not been systematically examined.

Use of NPPV in other patients with respiratory compromise, including asthma and pneumonia, is not well studied, though limited preliminary data suggest that NPPV may be beneficial for patients with acute asthma exacerbations.26–28 Studies have failed to establish a role for NPPV in pneumonia. Although no data suggest harm from NPPV, the presence of pneumonia has been shown to be an independent risk factor for failure of noninvasive ventilation.^29–32

Approach to Initial Ventilator Settings

Initial settings for noninvasive ventilation should be determined by the amount of ventilatory assistance required by the patient, as well as patient comfort and cooperation with the therapy. The first consideration in the use of NPPV is whether to provide support in the form of CPAP or BL-PAP. This was discussed earlier, and there is no clear benefit of one over the other. Support will be given by a full-face (oronasal) mask or nasal mask; this choice is determined by patient comfort, feelings of claustrophobia, and the need for the patient to effectively cough or speak. Inspiratory support (IPAP) can be initiated at 10 cm H₂O, and expiratory support (EPAP) can be initiated at 5 cm H₂O. Subsequent titration of these parameters is based on the patient’s clinical response, particularly pressure tolerance, respiratory rate, and oxyhemoglobin saturation. Though blood gas analysis is confirmatory, improvement in clinical condition can be observed by decrease in work of breathing, good patient-ventilator synchrony, and patient report. If required, EPAP and IPAP can be adjusted by 1 to 2 cm H₂O at a time based on clinical response.¹² If work of breathing is unchanged, increases in IPAP and EPAP reduce hypercarbia by increasing tidal volume and minute ventilation while increasing oxygenation by combating atelectasis and promoting alveolar recruitment. IPAP greater than 20 cm H₂O can be uncomfortable and can cause gastric insufflation and should be avoided.^12,33

For the intubated patient, initial ventilator settings should facilitate ventilation that improves gas exchange, promotes ventilatory synchrony, and minimizes the potential for complications. For an apneic or paralyzed patient, full ventilatory support is required; for this reason, A/C is the recommended mode of initial ventilation. Specific required settings depend on whether the patient is receiving PCV or VCV, but the principles underlying selection of settings are similar. Reasonable initial ventilator settings should deliver a tidal volume of 6 to 8 mL/kg of estimated ideal body weight (IBW) at rate of 12 to 14 breaths/min. If VCV is used, tidal volume can be set directly, and if PCV is used, tidal volume is determined by adjusting the targeted pressure to be delivered; initial pressure targets should not exceed 30 cm H₂O. Initial FIO₂ should be set at 1.0 but generally can be adjusted down quickly to maintain an oxygen saturation of 90% or greater. PEEP is routinely given and is set initially at 5 cm H₂O.⁶ Settings for specific clinical conditions, such as status asthmaticus, are discussed later.